Robust IgM responses following intravenous vaccination with Bacille Calmette-Guérin associate with prevention of Mycobacterium tuberculosis infection in macaques.
Administration, Intravenous
Animals
Antibodies, Bacterial
/ blood
BCG Vaccine
/ administration & dosage
Biomarkers
/ blood
Disease Models, Animal
Host-Pathogen Interactions
Immunogenicity, Vaccine
Immunoglobulin M
/ blood
Macaca mulatta
Mycobacterium tuberculosis
/ immunology
Time Factors
Tuberculosis
/ immunology
Vaccination
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
06
05
2021
accepted:
04
10
2021
pubmed:
24
11
2021
medline:
30
12
2021
entrez:
23
11
2021
Statut:
ppublish
Résumé
Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection against Mycobacterium tuberculosis (Mtb). Intravenous (i.v.) vaccination with Bacille Calmette-Guérin (BCG) provides nearly complete protection against TB in rhesus macaques, but the antibody response it elicits remains incompletely defined. Here we show that i.v. BCG drives superior antibody responses in the plasma and the lungs of rhesus macaques compared to traditional intradermal BCG administration. While i.v. BCG broadly expands antibody titers and functions, IgM titers in the plasma and lungs of immunized macaques are among the strongest markers of reduced bacterial burden. IgM was also enriched in macaques that received protective vaccination with an attenuated strain of Mtb. Finally, an Mtb-specific IgM monoclonal antibody reduced Mtb survival in vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and mediator of protection against TB.
Identifiants
pubmed: 34811542
doi: 10.1038/s41590-021-01066-1
pii: 10.1038/s41590-021-01066-1
pmc: PMC8642241
doi:
Substances chimiques
Antibodies, Bacterial
0
BCG Vaccine
0
Biomarkers
0
Immunoglobulin M
0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1515-1523Subventions
Organisme : NCI NIH HHS
ID : U54 CA225088
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00071
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI150171
Pays : United States
Organisme : NCI NIH HHS
ID : U2C CA233280
Pays : United States
Organisme : NCI NIH HHS
ID : U2C CA233262
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134240
Pays : United States
Organisme : NIH HHS
ID : P51 OD011133
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI138587
Pays : United States
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI152157
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021. The Author(s).
Références
World Health Organization. Global Tuberculosis Report 2020 (WHO, Geneva, 2020).
Fine, P. E. Variation in protection by BCG: implications of and for heterologous immunity. Lancet 346, 1339–1345 (1995).
pubmed: 7475776
doi: 10.1016/S0140-6736(95)92348-9
Caruso, A. M. et al. Mice deficient in CD4 T cells have only transiently diminished levels of IFN-γ, yet succumb to tuberculosis. J. Immunol. 162, 5407–5416 (1999).
pubmed: 10228018
doi: 10.4049/jimmunol.162.9.5407
Lin, P. L. et al. CD4 T cell depletion exacerbates acute Mycobacterium tuberculosis while reactivation of latent infection is dependent on severity of tissue depletion in cynomolgus macaques. AIDS Res. Hum. Retroviruses 28, 1693–1702 (2012).
pubmed: 22480184
pmcid: 3505050
doi: 10.1089/aid.2012.0028
Diedrich, C. R. et al. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load. PLoS ONE 5, e9611 (2010).
Esmail, H. et al. The immune response to Mycobacterium tuberculosis in HIV-1-coinfected persons. Annu. Rev. Immunol. 36, 603–638 (2018).
pubmed: 29490165
doi: 10.1146/annurev-immunol-042617-053420
Tameris, M. D. et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet 381, 1021–1028 (2013).
pubmed: 23391465
pmcid: 5424647
doi: 10.1016/S0140-6736(13)60177-4
Fletcher, H. A. et al. T cell activation is an immune correlate of risk in BCG vaccinated infants. Nat. Commun. 7, 11290 (2016).
pubmed: 27068708
pmcid: 4832066
doi: 10.1038/ncomms11290
Tait, D. R. et al. Final Analysis of a Trial of M72/AS01
pubmed: 31661198
doi: 10.1056/NEJMoa1909953
Nemes, E. et al. Prevention of M. tuberculosis infection with H4:IC31 vaccine or BCG revaccination. N. Engl. J. Med. 379, 138–149 (2018).
pubmed: 29996082
pmcid: 5937161
doi: 10.1056/NEJMoa1714021
Darrah, P. A. et al. Prevention of tuberculosis in macaques after intravenous BCG immunization. Nature 577, 95–102 (2020).
pubmed: 31894150
pmcid: 7015856
doi: 10.1038/s41586-019-1817-8
Brown, E. P. et al. High-throughput, multiplexed IgG subclassing of antigen-specific antibodies from clinical samples. J. Immunol. Methods 386, 117–123 (2012).
pubmed: 23023091
pmcid: 3475184
doi: 10.1016/j.jim.2012.09.007
Yang, H., Kruh-Garcia, N. A. & Dobos, K. M. Purified protein derivatives of tuberculin—past, present and future. FEMS Immunol. Med. Microbiol. 66, 273–280 (2012).
pubmed: 22762692
pmcid: 3491170
doi: 10.1111/j.1574-695X.2012.01002.x
Mishra, A. K., Driessen, N. N., Appelmelk, B. J. & Besra, G. S. Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction. FEMS Microbiol. Rev. 35, 1126–1157 (2011).
pubmed: 21521247
doi: 10.1111/j.1574-6976.2011.00276.x
Yuan, Y. et al. The 16-kDa alpha-crystallin (Acr) protein of Mycobacterium tuberculosis is required for growth in macrophages. Proc. Natl Acad. Sci. USA 95, 9578–9583 (1998).
pubmed: 9689123
pmcid: 21381
doi: 10.1073/pnas.95.16.9578
Esparza, M. et al. PstS-1, the 38-kDa Mycobacterium tuberculosis glycoprotein, is an adhesin, which binds the macrophage mannose receptor and promotes phagocytosis. Scand. J. Immunol. 81, 46–55 (2015).
pubmed: 25359607
doi: 10.1111/sji.12249
Ragas, A., Roussel, L., Puzo, G. & Rivière, M. The Mycobacterium tuberculosis cell-surface glycoprotein apa as a potential adhesin to colonize target cells via the innate immune system pulmonary C-type lectin surfactant protein A. J. Biol. Chem. 282, 5133–5142 (2007).
pubmed: 17158455
doi: 10.1074/jbc.M610183200
Hamasur, B. et al. A mycobacterial lipoarabinomannan specific monoclonal antibody and its F(ab') fragment prolong survival of mice infected with Mycobacterium tuberculosis. Clin. Exp. Immunol. 138, 30–38 (2004).
pubmed: 15373902
pmcid: 1809178
doi: 10.1111/j.1365-2249.2004.02593.x
Balu, S. et al. A novel human IgA monoclonal antibody protects against tuberculosis. J. Immunol. 186, 3113–3119 (2011).
pubmed: 21257971
doi: 10.4049/jimmunol.1003189
Watson, A. et al. Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis. Nat. Commun. 12, 602 (2021).
pubmed: 33504803
pmcid: 7840946
doi: 10.1038/s41467-021-20930-0
Lu, L. L. et al. IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure. Nat. Med. 25, 977–987 (2019).
pubmed: 31110348
pmcid: 6559862
doi: 10.1038/s41591-019-0441-3
Kunnath-Velayudhan, S. et al. Dynamic antibody responses to the Mycobacterium tuberculosis proteome. Proc. Natl Acad. Sci. USA 107, 14703–14708 (2010).
pubmed: 20668240
pmcid: 2930474
doi: 10.1073/pnas.1009080107
Pincetic, A. et al. Type I and type II Fc receptors regulate innate and adaptive immunity. Nat. Immunol. 15, 707–716 (2014).
pubmed: 25045879
pmcid: 7430760
doi: 10.1038/ni.2939
Alter, G., Malenfant, J. M. & Altfeld, M. CD107a as a functional marker for the identification of natural killer cell activity. J. Immunol. Methods 294, 15–22 (2004).
pubmed: 15604012
doi: 10.1016/j.jim.2004.08.008
Lu, L. L. et al. A functional role for antibodies in tuberculosis. Cell 167, 433–443 (2016).
pubmed: 27667685
pmcid: 5526202
doi: 10.1016/j.cell.2016.08.072
Martin, C. J. et al. Efferocytosis is an innate antibacterial mechanism. Cell Host Microbe 12, 289–300 (2012).
pubmed: 22980326
pmcid: 3517204
doi: 10.1016/j.chom.2012.06.010
Kaushal, D. et al. Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis. Nat. Commun. 6, 8533 (2015).
Achkar, J. M., Chan, J. & Casadevall, A. B cells and antibodies in the defense against Mycobacterium tuberculosis infection. Immunol. Rev. 264, 167–181 (2015).
pubmed: 25703559
pmcid: 4629253
doi: 10.1111/imr.12276
Choudhary, A. et al. Characterization of the antigenic heterogeneity of lipoarabinomannan, the major surface glycolipid of Mycobacterium tuberculosis, and complexity of antibody specificities toward this antigen. J. Immunol. 200, 3053–3066 (2018).
pubmed: 29610143
pmcid: 5911930
doi: 10.4049/jimmunol.1701673
Andreu, N. et al. Optimisation of bioluminescent reporters for use with mycobacteria. PLoS ONE 5, e10777 (2010).
pubmed: 20520722
pmcid: 2875389
doi: 10.1371/journal.pone.0010777
Plotkin, S. A. & Gilbert, P. B. Nomenclature for immune correlates of protection after vaccination. Clin. Infect. Dis. 54, 1615–1617 (2012).
pmcid: 3348952
doi: 10.1093/cid/cis238
Plotkin, S. A. Correlates of protection induced by vaccination. Clin. Vaccine Immunol. 17, 1055–1065 (2010).
pubmed: 20463105
pmcid: 2897268
doi: 10.1128/CVI.00131-10
Ehrenstein, M. R. & Notley, C. A. The importance of natural IgM: scavenger, protector and regulator. Nat. Rev. Immunol. 10, 778–786 (2010).
pubmed: 20948548
doi: 10.1038/nri2849
Klimovich, V. B. IgM and its receptors: structural and functional aspects. Biochem. 76, 534–549 (2011).
Meryk, A. et al. Fcμ receptor as a costimulatory molecule for T cells. Cell Rep. 26, 2681–2691 (2019).
pubmed: 30840890
doi: 10.1016/j.celrep.2019.02.024
Dijkman, K. et al. Prevention of tuberculosis infection and disease by local BCG in repeatedly exposed rhesus macaques. Nat. Med. 25, 255–262 (2019).
pubmed: 30664782
doi: 10.1038/s41591-018-0319-9
Balasubramanian, V., Wiegeshaus, E. H., Taylor, B. T. & Smith, D. W. Pathogenesis of tuberculosis: pathway to apical localization. Tuber. Lung Dis. 75, 168–178 (1994).
pubmed: 7919306
doi: 10.1016/0962-8479(94)90002-7
Allie, S. R. et al. The establishment of resident memory B cells in the lung requires local antigen encounter. Nat. Immunol. 20, 97–108 (2019).
pubmed: 30510223
doi: 10.1038/s41590-018-0260-6
Onodera, T. et al. Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection. Proc. Natl Acad. Sci. USA 109, 2485–2490 (2012).
pubmed: 22308386
pmcid: 3289300
doi: 10.1073/pnas.1115369109
Cirovic, B. et al. BCG vaccination in humans elicits trained immunity via the hematopoietic progenitor compartment. Cell Host Microbe 28, 322–334 (2020).
pubmed: 32544459
pmcid: 7295478
doi: 10.1016/j.chom.2020.05.014
Kaufmann, E. et al. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172, 176–190 (2018).
pubmed: 29328912
doi: 10.1016/j.cell.2017.12.031
Boruchov, A. M. et al. Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. J. Clin. Invest. 115, 2914–2923 (2005).
pmcid: 1201664
doi: 10.1172/JCI24772
Guilliams, M., Bruhns, P., Saeys, Y., Hammad, H. & Lambrecht, B. N. The function of Fcγ receptors in dendritic cells and macrophages. Nat. Rev. Immunol. 142, 94–108 (2014).
doi: 10.1038/nri3582
Hoffmann, E. et al. Autonomous phagosomal degradation and antigen presentation in dendritic cells. Proc. Natl Acad. Sci. USA 109, 14556–14561 (2012).
pubmed: 22908282
pmcid: 3437883
doi: 10.1073/pnas.1203912109
Schlottmann, S. A., Jain, N., Chirmule, N. & Esser, M. T. A novel chemistry for conjugating pneumococcal polysaccharides to Luminex microspheres. J. Immunol. Methods 309, 75–85 (2006).
pubmed: 16448665
doi: 10.1016/j.jim.2005.11.019
van Woudenbergh, E. et al. HIV is associated with modified humoral immune responses in the setting of HIV/TB coinfection. mSphere 5, e00104-20 (2020).
pubmed: 32434838
pmcid: 7380575
doi: 10.1128/mSphere.00104-20
Brown, E. P. et al. Multiplexed Fc array for evaluation of antigen-specific antibody effector profiles. J. Immunol. Methods 443, 33–44 (2017).
pubmed: 28163018
pmcid: 5333794
doi: 10.1016/j.jim.2017.01.010
Karsten, C. B. et al. A versatile high-throughput assay to characterize antibody-mediated neutrophil phagocytosis. J. Immunol. Methods 471, 46–56 (2019).
pubmed: 31132351
pmcid: 6620195
doi: 10.1016/j.jim.2019.05.006
Rohart, F., Gautier, B., Singh, A. & Lê Cao, K.-A. mixOmics: an R package for 'omics feature selection and multiple data integration. PLoS Comput. Biol. 13, e1005752 (2017).
pubmed: 29099853
pmcid: 5687754
doi: 10.1371/journal.pcbi.1005752
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B 57, 289–300 (1995).